Pyruvate improves cardiac electromechanical and metabolic recovery from cardiopulmonary arrest and resuscitation

Sharma, Arti B.; Knott, E. Marty; Bi, Jian; Martinez, R; Sun, Jie; Mallet, Robert T.

doi:10.1016/j.resuscitation.2004.12.016

Cited by 28 publications

(39 citation statements)

References 34 publications

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“…Pyruvate is a molecule central to delivering energy to the body cells, and the metabolism is under control of a range of different physiological conditions (20)(21)(22). Despite this control, it is possible to create metabolic images of 13 C-lacate and 13 C-alanine within a minute after injection of supraphysiological levels of 13 C-pyruvate.…”

Section: Resultsmentioning

confidence: 99%

Real-time metabolic imaging

Golman¹,

Zandt²,

Thaning³

2006

Proc. Natl. Acad. Sci. U.S.A.

630

847

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The endogenous substance pyruvate is of major importance to maintain energy homeostasis in the cells and provides a window to several important metabolic processes essential to cell survival. Cell viability is therefore reflected in the metabolism of pyruvate. NMR spectroscopy has until now been the only noninvasive method to gain insight into the fate of pyruvate in the body, but the low NMR sensitivity even at high field strength has only allowed information about steady-state conditions. The medically relevant information about the distribution, localization, and metabolic rate of the substance during the first minute after the injection has not been obtainable. Use of a hyperpolarization technique has enabled 10 -15% polarization of 13 C1 in up to a 0.3 M pyruvate solution. i.v. injection of the solution into rats and pigs allows imaging of the distribution of pyruvate and mapping of its major metabolites lactate and alanine within a time frame of Ϸ10 s. Real-time molecular imaging with MRI has become a reality.13 C ͉ dynamic nuclear polarization ͉ hyperpolarized ͉ MRI ͉ spectroscopy T he technique for increase in signal-to-noise ratio of Ͼ10,000 times in liquid-state NMR and the use of this technique for molecular imaging with endogenous substances generated through the process of dynamic nuclear polarization (DNP) has been reported (1, 2). In both these studies, 13 C-enriched urea was used as an example of an endogenous substance that could be polarized to a high degree (37% for 13 C and 8% for 15 N) and used for high-resolution imaging of the cardiovascular system in rats.It was suggested that the signal enhancement could be used not only for visualizing the cardiovascular system but also for improved perfusion measurements and that it may allow realtime metabolic mapping of other endogenous substances such as alanine, glutamine, and acetate. Such studies should be possible if the relaxation time of the 13 C-labeled site in the hyperpolarized molecule is long enough and the metabolic products retain sufficient fraction of the nonequilibrium polarization. The possibilities for doing perfusion studies using 13 C labeled hyperpolarized substances have recently been reviewed by Månsson et al. (3), but the application of visualizing metabolic processes by using hyperpolarized substances have not yet been described.To reveal information about the metabolic status of the tissue, magnetic resonance (MR) spectroscopy has been used, employing nuclei like 1 H, 13 C, 31 P, and 19 F (4, 5). The main application areas have been brain, muscle, and prostate tissue. Information on fluxes through metabolic pathways is less straightforward to obtain though. Traditionally, 13 C NMR spectroscopy in combination with 13 C-labeled (enriched) substrates has been used to visualize the label applied, its metabolic intermediates, and͞or its end products during steady-state conditions. In certain cases the metabolic rates can be indirectly estimated by using mathematical modeling (6), for example, in determining the flux through the...

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Section: Resultsmentioning

confidence: 99%

Real-time metabolic imaging

Golman¹,

Zandt²,

Thaning³

2006

Proc. Natl. Acad. Sci. U.S.A.

630

847

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“…Twentythree mongrel dogs weighing 22 ± 4 kg were randomly assigned to sham (3♂, 3♀), pyruvate (4♂, 5♀) or vehicle control NaCl (4♂, 4♀) groups. Pyruvate and NaCl groups underwent an open chest cardiac arrest-CPR-defibrillation protocol 17 under sterile conditions. The experimenters conducting CPR protocol were blinded to the treatments administered.…”

Section: Instrumentation and Protocol Surgerymentioning

confidence: 99%

“…13 Pyruvate readily traverses the blood brain barrier via monocarboxylate transporters 14 and provides an excellent energy substrate for neurons and astroglia. 15 Pyruvate's antiacidotic, 16,17 antiinflammatory 18 and anti-apoptotic 19 properties could minimize neuronal death following cerebral ischemia-reperfusion. Indeed, pyruvate treatment preserves neurons following exposure to oxidants.…”

Section: Introductionmentioning

confidence: 99%

Pyruvate enhances neurological recovery following cardiopulmonary arrest and resuscitation

et al. 2008

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Purpose-Cerebral oxidative stress and metabolic dysfunction impede neurological recovery from cardiac arrest-resuscitation. Pyruvate, a potent antioxidant and energy-yielding fuel, has been shown to protect against oxidant-and ischemia-induced neuronal damage. This study tested whether acute pyruvate treatment during cardiopulmonary resuscitation can prevent neurological dysfunction and cerebral injury following cardiac arrest. Methods-Anesthetized, open-chest mongrel dogs underwent 5 min cardiac arrest, 5 min open chest cardiac compression (OCCC), defibrillation and 3 day recovery. Pyruvate (n = 9) or NaCl volume control (n = 8) were administered (0.125 mmol/kg/min iv) throughout OCCC and the first 55 min recovery. Sham dogs (n = 6) underwent surgery and recovery without cardiac arrestresuscitation.Results-Neurological deficit score (NDS), evaluated at 2 day recovery, was sharply increased in NaCl-treated dogs (10.3 ± 3.5) vs. shams (1.2 ± 0.4), but pyruvate treatment mitigated neurological deficit (NDS = 3.3 ± 1.2; P < 0.05 vs. NaCl). Brain samples were taken for histological examination and evaluation of inflammation and cell death at 3 d recovery. Loss of pyramidal neurons in the hippocampal CA1 subregion was greater in the NaCl controls than in pyruvate treated dogs (11.7 ± 2.3% vs. 4.3 ± 1.2%; P < 0.05). Cardiac arrest increased caspase 3 activity, matrix metalloproteinase activity, and DNA fragmentation in the CA1 subregion; pyruvate prevented caspase-3 activation and DNA fragmentation, and suppressed matrix metalloproteinase activity.Conclusion-Intravenous pyruvate therapy during cardiopulmonary resuscitation prevents initial oxidative stress and neuronal injury and enhances neurological recovery from cardiac arrest.

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“…Thus, the temporal variability of repolarization produced by oxyradical attack on various cardiac ion channels can place the myocardium in a proarrhythmic state. Pyruvate supplementation can prevent ST segment elevation in myocardial ischemia-reperfusion [55,56] , but pyruvate's influence on cardiac repolarization has not been reported. In this study, pyruvate-enriched resuscitation prevented the increased instability of repolarization produced by lactated Ringer's resuscitation following hypovolemia and hindlimb ischemia-reperfusion.…”

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confidence: 96%

Pyruvate-fortified resuscitation stabilizes cardiac electrical activity and energy metabolism during hypovolemia

Gurji

White

Hoxha

et al. 2013

WJCCM

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AIM:To test the hypothesis that fluid resuscitation with Ringer's solution enriched with pyruvate (PR), a physiological antioxidant and energy substrate, affords protection of myocardial metabolism and electrophysiological performance superior to lactated Ringer's (LR) during hypovolemia and hindlimb ischemia-reperfusion. METHODS:Male domestic goats (25-30 kg) were exsanguinated to a mean arterial pressure of 48 ± 1 mmHg. Right hindlimb ischemia was imposed for 90 min by applying a tourniquet and femoral crossclamp.LR or PR, infused iv , delivered 0.05 mmol/kg per minute L -lactate or pyruvate, respectively, from 30 min hindlimb ischemia until 30 min post-ischemia. Time controls (TC) underwent neither hemorrhage, hindlimb ischemia nor resuscitation. Goats were sacrificed and left ventricular myocardium biopsied at 90 min fluid resuscitation (n = 6 per group) or 3.5 h later (n = 9 LR, 10 PR, 8 TC). RESULTS:Myocardial 8-isoprostane content, phosphocreatine phosphorylation potential, creatine kinase activity, and heart rate-adjusted QT interval (QTc) variability were evaluated at 90 min resuscitation and 3.5 h post-resuscitation. PR sharply lowered pro-arrhythmic QTc variability vs LR (P < 0.05); this effect persisted 3.5 h post-resuscitation. PR lowered myocardial 8-isoprostane content, a product of oxidative stress, by 39 and 37% during and 3.5 h after resuscitation, respectively, vs LR. Creatine kinase activity fell 42% post-LR vs TC (P < 0.05), but was stable post-PR (P < 0.02 vs post-LR).PR doubled phosphocreatine phosphorylation potential, a measure of ATP free energy state, vs TC and LR (P < 0.05); this energetic enhancement persisted 3.5 h post-resuscitation. Core tip: In goats subjected to exsanguination-induced hypovolemia and tourniquet-imposed hindlimb ischemia-reperfusion, intravenous resuscitation with Ringer's lactate produced marked electrocardiographic instability, lipid peroxidation and inactivation of the critical creatine kinase system, which supplies energy for membrane ion transport. In comparison with lactated Ringer's, resuscitation enriched with the natural antioxidant and energy substrate pyruvate stabilized cardiac rhythm, prevented lipid peroxidation, preserved creatine kinase activity and augmented myocardial energy reserves. Importantly, these favorable effects persisted for at least 3.5 h after terminating pyruvateenriched resuscitation. Thus, pyruvate-enriched resuscitation prevented creatine kinase inactivation by oxidative stress, thereby preventing cardiac rhythm disturbances after central hypovolemia. CONCLUSION:Gurji HA, White DW, Hoxha B, Sun J, Olivencia-Yurvati AH, Mallet RT. Pyruvate-fortified resuscitation stabilizes cardiac electrical activity and energy metabolism during hypovolemia. World J Crit Care Med 2013; 2(4): 56-64 Available from: URL:

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Pyruvate improves cardiac electromechanical and metabolic recovery from cardiopulmonary arrest and resuscitation

Cited by 28 publications

References 34 publications

Real-time metabolic imaging

Real-time metabolic imaging

Pyruvate enhances neurological recovery following cardiopulmonary arrest and resuscitation

Pyruvate-fortified resuscitation stabilizes cardiac electrical activity and energy metabolism during hypovolemia

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